Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

Detalhes bibliográficos
Autor(a) principal: Machado-Neto, João Agostinho
Data de Publicação: 2019
Outros Autores: Fenerich, Bruna Alves, Alves, Ana Paula Nunes Rodrigues, Fernandes, aqueline Cristina, Scopim-Ribeiro, Renata, Coelho-Silva, Juan Luiz, Traina, Fabiola
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Clinics
Texto Completo: https://www.revistas.usp.br/clinics/article/view/154888
Resumo: The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.
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spelling Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesisInsulin Receptor SubstrateAdaptor ProteinSignal TransductionHematopoiesisLeukemiaMyeloproliferative NeoplasmsThe insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2019-02-18info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/15488810.6061/clinics/2018/e566sClinics; Vol. 73 No. Suppl. 1 (2018); e566sClinics; v. 73 n. Suppl. 1 (2018); e566sClinics; Vol. 73 Núm. Suppl. 1 (2018); e566s1980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/154888/150805Copyright (c) 2019 Clinicsinfo:eu-repo/semantics/openAccessMachado-Neto, João AgostinhoFenerich, Bruna AlvesAlves, Ana Paula Nunes RodriguesFernandes, aqueline CristinaScopim-Ribeiro, RenataCoelho-Silva, Juan LuizTraina, Fabiola2019-05-14T11:48:25Zoai:revistas.usp.br:article/154888Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2019-05-14T11:48:25Clinics - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
title Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
spellingShingle Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
Machado-Neto, João Agostinho
Insulin Receptor Substrate
Adaptor Protein
Signal Transduction
Hematopoiesis
Leukemia
Myeloproliferative Neoplasms
title_short Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
title_full Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
title_fullStr Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
title_full_unstemmed Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
title_sort Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
author Machado-Neto, João Agostinho
author_facet Machado-Neto, João Agostinho
Fenerich, Bruna Alves
Alves, Ana Paula Nunes Rodrigues
Fernandes, aqueline Cristina
Scopim-Ribeiro, Renata
Coelho-Silva, Juan Luiz
Traina, Fabiola
author_role author
author2 Fenerich, Bruna Alves
Alves, Ana Paula Nunes Rodrigues
Fernandes, aqueline Cristina
Scopim-Ribeiro, Renata
Coelho-Silva, Juan Luiz
Traina, Fabiola
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Machado-Neto, João Agostinho
Fenerich, Bruna Alves
Alves, Ana Paula Nunes Rodrigues
Fernandes, aqueline Cristina
Scopim-Ribeiro, Renata
Coelho-Silva, Juan Luiz
Traina, Fabiola
dc.subject.por.fl_str_mv Insulin Receptor Substrate
Adaptor Protein
Signal Transduction
Hematopoiesis
Leukemia
Myeloproliferative Neoplasms
topic Insulin Receptor Substrate
Adaptor Protein
Signal Transduction
Hematopoiesis
Leukemia
Myeloproliferative Neoplasms
description The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.
publishDate 2019
dc.date.none.fl_str_mv 2019-02-18
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/clinics/article/view/154888
10.6061/clinics/2018/e566s
url https://www.revistas.usp.br/clinics/article/view/154888
identifier_str_mv 10.6061/clinics/2018/e566s
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/clinics/article/view/154888/150805
dc.rights.driver.fl_str_mv Copyright (c) 2019 Clinics
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2019 Clinics
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
dc.source.none.fl_str_mv Clinics; Vol. 73 No. Suppl. 1 (2018); e566s
Clinics; v. 73 n. Suppl. 1 (2018); e566s
Clinics; Vol. 73 Núm. Suppl. 1 (2018); e566s
1980-5322
1807-5932
reponame:Clinics
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Clinics
collection Clinics
repository.name.fl_str_mv Clinics - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||clinics@hc.fm.usp.br
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